High-risk Patients Research Articles

Real-World Effectiveness of Nirmatrelvir in Protecting Long COVID for Outpatient Adult Patients - A Large-Scale Observational Cohort Study from the RECOVER Initiative.

Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30-180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 1, 2023, and among which 165,256 were treated with Paxlovid within 5 days since infection and 307,922 were not treated with Paxlovid or other COVID-19 treatments. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). Paxlovid treatment was associated with reduced risk of all-cause death (HR, 0.53, 95% CI 0.46 to 0.60; risk reduction 0.23 events per 100 persons, 95% CI 0.19 to 0.28) and hospitalization (HR, 0.70, 95% CI 0.68 to 0.73; risk reduction 2.37 events per 100 persons, 95% CI 2.19 to 2.56) in the post-acute phase. For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. Overall, high-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.

Outcomes of endoscopic ultrasound-guided gallbladder drainage: A multicenter study from India (with video).

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) offers a safe and minimally invasive alternative for percutaneous cholecystostomy (PCC) in acute cholecystitis patients with high-surgical risk. Additionally, EUS-GBD serves as a rescue biliary drainage in malignant distal biliary obstruction. Despite its widespread application, data within the Indian context remains sparse. This study aims to report the outcomes of EUS-GBD through the first multi-center study from India. We retrospectively analyzed patients undergoing EUS-GBD at six tertiary care centers of India from March 2022 to November 2023. EUS-GBD was performed by free hand or over-the-guidewire technique with lumen-apposing metal stent (LAMS) or large caliber metal stent (LCMS). The primary outcome was technical success (defined as successful deployment of stent between gallbladder and stomach/duodenal lumen). The secondary outcomes were clinical success (defined as resolution of symptoms of acute cholecystitis and more than > 50% reduction in bilirubin level within two weeks in distal biliary obstruction), adverse event rate, 30-day mortality rate and 90-day reintervention rate. Total29 patients (mean age 65.86 ± 12.91, 11 female) underwent EUS-GBD. The indication for EUS-GBD were acute cholecystitis (79.31%) and rescue biliary drainage for malignant distal biliary obstruction (20.69%). LAMS was deployed in 92.86%, predominantly by free-hand technique (78.57%). Technical and clinical success rates were 96.55% and 82.75%, respectively. Adverse events occurred in 27.59% patients, with severe adverse events (bile leak and bleeding) being uncommon (10%). Both 30-day mortality rate and 90-day reintervention rate were 13.79% in patients. Cholecysto-duodenal fistula facilitated cholecystoscopic intervention and stone removal in one patient and transgastric EUS-GBD did not hamper bilio-enteric anastomosis during Whipple surgery in two patients. EUS-GBD is a safe and effective technique for managing acute cholecystitis in high-risk patients and for biliary drainage in cases with malignant distal biliary obstruction.

Radiomics based on HRCT can predict RP-ILD and mortality in anti-MDA5 + dermatomyositis patients: a multi-center retrospective study

ObjectivesTo assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD).MethodsFrom August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression.ResultsOver a median follow-up time of 31.6 months (interquartile range: 12.9–49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515).ConclusionFor anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.

Development and validation of a deep learning model for predicting gastric cancer recurrence based on CT Imaging: a multicenter study.

The postoperative recurrence of gastric cancer has a significant impact on the overall prognosis of patients. Therefore, accurately predicting the postoperative recurrence of gastric cancer is crucial. This retrospective study gathered data from 2,813 gastric cancer patients who underwent radical surgery between 2011 and 2017 at two medical centers. Follow-up was extended until May 2023, and cases were categorized as recurrent or non-recurrent based on postoperative outcomes. Clinical pathological information and imaging data were collected for all patients. A new deep learning signature (DLS) was generated using pretreatment CT images, based on a pre-trained baseline (a customized Resnet50), for predicting postoperative recurrence. The deep learning fusion signature (DLFS) was created by combining the score of DLS with the weighted values of identified clinical features. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. Survival curves were plotted to investigate the differences between DLFS and prognosis. In this study, 2813 patients with gastric cancer (GC) were recruited and allocated into training, internal validation, and external validation cohorts. The DLFS was developed and assessed for its capability in predicting the risk of postoperative recurrence. The DLFS exhibited excellent performance with AUCs of 0.833 (95% CI, 0.809-0.858) in the training set, 0.831 (95% CI, 0.792-0.871) in the internal validation set, and 0.859 (95% CI, 0.806-0.912) in the external validation set, along with satisfactory calibration across all cohorts (P>0.05). Furthermore, the DLFS model significantly outperformed both the clinical model and DLS (P<0.05). High-risk recurrent patients exhibit a significantly poorer prognosis compared to low-risk recurrent patients (P<0.05). The integrated model developed in this study, focusing on GC patients undergoing radical surgery, accurately identifies cases at high risk of postoperative recurrence and highlights the potential of DLFS as a prognostic factor for GC patients.

Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer

BackgroundThe IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual’s cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1–<5%), intermediate-risk (5–<20%), and high-risk (≥20%) groups. ObjectiveTo externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. Design, setting, and participantsProspective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. Outcome measurements and statistical analysisThe area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. Results and limitationsThere were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. ConclusionsThe IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. Patient summaryWe previously developed a calculator that predicts patients’ risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

Preoperative sequential chemotherapy and hypofractionated radiotherapy combined with comprehensive surgical resection for high-risk soft tissue sarcomas: a retrospective study.

The management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential chemotherapy and hypofractionated radiotherapy in conjunction with extensive surgical resection for the treatment of high-risk soft tissue sarcomas. We performed a retrospective review of 31 high-risk soft tissue sarcoma patients treated at our institution from June 2021 to June 2023. The cohort consisted of 21 males and 10 females with a mean age of 55.7 years and included both initial and recurrent disease presentations. Our treatment regimen comprised two to three cycles of neoadjuvant chemotherapy coupled with hypofractionated radiotherapy, delivered at 5 Gy per fraction to a total dose of 25-35 Gy across 5-7 days, prior to surgical resection aimed at achieving wide margins. Data collection was systematic, covering surgical outcomes, chemoradiotherapy-related complications, and prognostic factors. All patients completed the prescribed course of neoadjuvant chemoradiotherapy. 29% patients experienced grade 3+ chemotherapy toxicity, necessitating a reduction or interruption in their chemotherapy regimen. Limb preservation was accomplished in 30 patients finally. Response evaluation using RECIST 1.1 criteria post-neoadjuvant therapy revealed 9.7% with PD, 58.1% with SD, 29% with a PR, and 3.2% with a CR, culminating in an ORR of 32.2%. Postoperative complications included superficial wound infections in four patients and deep incisional infections in another four. 6 patients had developed metastasis, and 3 patients were still alive. Two experienced local recurrence. One-year DFS was 79.3%, with a one-year OS rate of 89.6%. Neoadjuvant sequential chemotherapy and hypofractionated radiotherapy followed by extensive surgical resection represents an effective treatment paradigm for high-risk soft tissue sarcomas. This multimodal approach not only facilitates tumor reduction but also significantly reduces the risks of local recurrence and distant metastasis.

An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs

BackgroundNeuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models.ResultsHere, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We develop an unsupervised machine learning approach (“automatic consensus nonnegative matrix factorization” (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirm a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly, however, this weak-mesenchymal-like program is maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 h, suggesting an uncharacterized therapy-escape mechanism.ConclusionsCollectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets.

CETP and SGLT2 inhibitor combination therapy increases glycemic control: a 2x2 factorial Mendelian randomization analysis.

Cholesteryl ester transfer protein (CETP) inhibitors, initially developed for treating hyperlipidemia, have shown promise in reducing the risk of new-onset diabetes during clinical trials. This positions CETP inhibitors as potential candidates for repurposing in metabolic disease treatment. Given their oral administration, they could complement existing oral medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors, potentially delaying the need for injectable therapies such as insulin. We conducted a 2x2 factorial Mendelian Randomization analysis involving 233,765 participants from the UK Biobank. This study aimed to evaluate whether simultaneous genetic inhibition of CETP and SGLT2 enhances glycemic control compared to inhibiting each separately. Our findings indicate that dual genetic inhibition of CETP and SGLT2 significantly reduces glycated hemoglobin levels compared to controls and single-agent inhibition. Additionally, the combined inhibition is linked to a lower incidence of diabetes compared to both the control group and SGLT2 inhibition alone. These results suggest that combining CETP and SGLT2 inhibitor therapies may offer superior glycemic control over SGLT2 inhibitors alone. Future clinical trials should investigate the potential of repurposing CETP inhibitors for metabolic disease treatment, providing an oral therapeutic option that could benefit high-risk patients before they require injectable therapies like insulin or glucagon-like peptide-1 (GLP-1) receptor agonists.

Abstract PO-023: CD70 deregulation in follicular lymphoma at diagnosis is associated with relapse and opens new avenues for dual CD19-CD70 CAR-T therapy

Abstract Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Despite most patients achieve a complete response with first-line treatment, an important fraction of them relapse, which may worsen the prognosis and increase the risk of a histological transformation to aggressive lymphoma. Therefore, there is a need to better stratify the patients at the diagnosis and develop tailored therapies for high-risk patients. Here we have assessed the immune profile (Nanostring® nCounter) in FFPE-derived biopsies in a series of FL patients at diagnosis, homogenously treated with immunochemotherapy regimen (mostly R-CHOP), and followed-up at Hospital Clínic de Barcelona for more than 12 years. By comparing patients who experienced relapse (n=20) with those who did not relapse at any time (NR, n=12), we have found 31 differentially expressed genes, 25 of them up-regulated in the relapse group. Among them, we have further focused on the role of CD70 in FL pathogenesis. mRNA CD70 was higher in those patients who eventually relapsed and correlated with inferior PFS. Moreover, CD70high FL cases bear a limited number of recurrent somatic mutations. We next sought to determine the specific subpopulations expressing CD70 by multiplex immunofluorescence (Vectra Polaris). Interestingly, we have demonstrated it is mainly expressed in tumor cells correlating with inferior PFS. Moreover, a fraction of T cells from the tumor microenvironment also expresses CD70. Intriguingly, higher levels of CD70 were detected in both CD4+ and CD8+ T cells in the relapse group, including T regulatory and T follicular helper cells. CD70 interacts with CD27, its only known ligand, and can be mutually activated. While CD27 RNA levels did not change between groups, CD27 protein was increased in the B cell population in patients who eventually relapse and in TFH cells, while it was down-regulated in CD8+ and CD4+ T helper non-follicular cells. Furthermore, we found an association between the percentage of CD70+ cells within B cell population and CD70+ in CD4+ and CD8+ cells (R=0.51, p &amp;lt; 0.05). To investigate the role of CD70 in FL pathogenesis we generated two CD70 KO cell lines and FL patient derived cells (n=4) using CRISPR/Cas9 technique. By co-culturing T cells from healthy donors with CD70+ or CD70- FL cell lines, we observed CD70+ tumor cells promote CD70 expression in T cells. In primary samples, we have demonstrated that CD70-KO B cells exhibit reduced response to proliferative stimuli. Moreover, RNAseq analysis followed by GSEA pathway assignment indicated that CD70 expression was related to increased angiogenesis, glycolysis and hypoxia. Finally, to advance towards personalized therapies for this high-risk patient and taking advantage of our institution CAR-T program, we have generated a dual CD19-CD70 CAR-T combining an approved academic product, ARI-0001, and a truncated CD27 protein. Finally, we have demonstrated that this novel CAR-T is effective in both cell lines and ex vivo FL spheroids (PDLS, Dobaño-López, Blood Cancer J 2024), while in vivo studies are ongoing. Citation Format: Ferran Araujo-Ayala, Mireia Bachiller, Raluca Alexandru, Pablo Mozas, Salut Colell, María Villalba-Esparza, Judith Mateos-Jaimez, Ferran Nadeu, Andrea Rivero, Maria Ros, Cèlia Dobaño-López, Juan Garcia Valero, Neus Serrat, Marta Gimenez-Alejandre, Ariadna Giro, Daniel Hodson, Armando López-Guillermo, Elias Campo, Dolors Colomer, Alba Maiques-Diaz, José Ignacio Martín-Subero, Sílvia Beà, Laura Magnano, Sonia Guedan, Carlos E. de Andrea, Patricia Pérez-Galan. CD70 deregulation in follicular lymphoma at diagnosis is associated with relapse and opens new avenues for dual CD19-CD70 CAR-T therapy [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-023.

Abdominal Hypoperfusion and Acute Kidney Injury in the Critically Ill Patient with Liver Cirrhosis: A Prospective Cohort Study

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Reduced abdominal perfusion pressure (APP) is an underdiagnosed potential pathophysiological mechanism for acute kidney injury (AKI) in the patient with liver cirrhosis and ascites. This study aimed to analyze the prevalence of abdominal hypoperfusion (AhP) (APP &amp;lt;60 mm Hg) and the impact of APP on AKI in critically ill patients with liver cirrhosis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This was a post hoc analysis from a prospective cohort study set in a general ICU at a tertiary university hospital. Patients were recruited between October 2016 and December 2021. Acute renal failure (ARF) was defined by stage 3 AKI according to the International Club of Ascites. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Fifty-eight patients where included, with a mean age of 57 (±8.4) years, 79% were male, and 93% had acute-on-chronic liver failure at admission. The prevalence of AhP reached 75%, and 29% of cases had persisting AhP during the first week of ICU stay. Patients with baseline AhP had a higher 28-day mortality compared to those without AhP (respectively, 76% vs. 49%, &lt;i&gt;p&lt;/i&gt; = 0.03). Acute renal failure developed in 48% of patients. Higher serum urea (aOR: 1.01, 95% CI: 1.00–1.02, &lt;i&gt;p&lt;/i&gt; = 0.04) and white blood cell count (aOR: 1.1, 95% CI: 1.01–1.2, &lt;i&gt;p&lt;/i&gt; = 0.02) at ICU admission, as well as low persisting APP (aOR: 0.9, 95% CI: 0.86–0.98, &lt;i&gt;p&lt;/i&gt; = 0.02) were independent risk factors for ARF. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Critically ill patients with liver cirrhosis presented a high prevalence of ARF, independently associated with higher baseline serum urea and WBC, and lower persisting APP. A structured clinical approach to optimize APP may reduce renal dysfunction in high-risk patients with cirrhosis.

MDB-70. SYSTEMATIC TRANSCRIPTOMIC ANALYSIS OF CHILDHOOD MEDULLOBLASTOMA IDENTIFIES M6A-LNCRNA SIGNATURES ASSOCIATED WITH PROGNOSIS, MOLECULAR SUBTYPE, AND IMMUNE CELL INFILTRATION

Abstract BACKGROUND Medulloblastoma (MB) is the predominant pediatric brain tumor, subdivided into four molecular subgroups, with group 3 and group 4 tumors posing significant clinical challenges due to poor prognosis and classification. This study investigates the roles of N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) in MB, aiming to develop diagnostic and prognostic tools. METHODS We analyzed transcriptome from 1236 samples to identify m6A-associated lncRNA signature (M6LSig). A multivariate-cox analysis identified a gene signature significantly associated with overall survival (OS) of patients. Risk score was calculated based on the sum of weighted gene expression of these genes. Nomograms were calculated for predicting OS and PFS probability. We did feature selection with Boruta to identify minimum gene signature for subgroup classification. We performed correlation analysis of gene signature and risk score with immune-cell abundance. We depleted METTL3 and METTL14 in G3-MB cell-line (D425) to measure impact on cell proliferation and dysregulation of M6LSig genes as a result of loss of m6A. RESULTS Nomogram was constructed using risk score derived from 24 M6LSig significantly associated with OS and PFS of the patients. A 171 gene signature was identified that can accurately classify samples into one of four major subgroups of MB with more than 90% accuracy including between Grp3/Grp4 samples. M6LSig genes and risk score showed significant correlation with immune cell type abundance in MB tumors. Expression of CD155 and 4-1BB was significantly different between high and low risk samples. m6A writer genes knockdown in D425 cells resulted in decreased cell proliferation and upregulation of many M6LSig genes. CONCLUSION M6LSig based risk can accurately predict OS and PFS and 171 genes signature can classify patients into subgroups with more than 90% accuracy. Risk score can also be used for determining high risk versus low-risk patient and design tailor made immune-therapy for better survival.

Optimizing Surgical Outcomes and the Role of Preventive Surgery: A Scoping Review.

Plastic and reconstructive surgeons are often presented with reconstructive challenges as a sequela of complications in high-risk surgical patients, ranging from exposure of hardware, lymphedema, and chronic pain after amputation. These complications can result in significant morbidity, recovery time, resource utilization, and cost. Given the prevalence of surgical complications managed by plastic and reconstructive surgeons, developing novel preventative techniques to mitigate surgical risk is paramount. Herein, we aim to understand efforts supporting the nascent field of Preventive Surgery, including (1) enhanced risk stratification, (2) advancements in postoperative care. Through an emphasis on four surgical cohorts who may benefit from preventive surgery, two of which are at high risk of morbidity from wound-related complications (patients undergoing sternotomy and spine procedures) and two at high risk of other morbidities, including lymphedema and neuropathic pain, we aim to provide a comprehensive and improved understanding of preventive surgery. Additionally, the role of risk analysis for these procedures and the relationship between microsurgery and prophylaxis is emphasized. (1) medical optimization and prehabilitation, (2) surgical mitigation techniques. Reconstructive surgeons are ideally placed to lead efforts in the creation and validation of accurate risk assessment tools and to support algorithmic approaches to surgical risk mitigation. Through a paradigm shift, including universal promotion of the concept of "Preventive Surgery," major improvements in surgical outcomes may be achieved.

In-Hospital Outcomes of Patients with Anterior Wall Myocardial Infarction and Right Bundle Branch Block in the Primary PCI Era: Impact and Prognostic Factors

Objective: This study investigates the in-hospital outcomes of patients presenting with Anterior Wall Myocardial Infarction (AWMI) and Right Bundle Branch Block (RBBB) during the primary Percutaneous Coronary Intervention (PCI) era. It aims to assess the impact of primary PCI on these patients and identify factors contributing to poor outcomes. Methodology: A prospective observational study was conducted at the Department of Cardiology, Hayatabad Medical Complex (HMC), Peshawar, Pakistan. The study enrolled 150 patients diagnosed with AWMI and RBBB, undergoing reperfusion therapy. Data on demographics, clinical characteristics, and treatment outcomes were collected and analyzed using IBM SPSS version 21.0. Results: Among the 150 patients included in the study, there was a balanced gender distribution with a mean age of 51.15 years. The majority of patients, 136 (90.7%), survived their hospital stay. Primary PCI was significantly associated with improved survival rates compared to medical management alone. Factors such as TIMI and GRACE risk scores were crucial for risk stratification, highlighting the need for personalized management strategies. Conclusion: The findings underscore the effectiveness of primary PCI in improving in-hospital outcomes for patients with AWMI and RBBB. This study highlights the necessity of timely reperfusion therapy and personalized risk stratification to enhance patient prognosis. By documenting the impact of primary PCI and identifying factors leading to poor outcomes, this research provides valuable insights that aid in the optimization of treatment protocols for this high-risk patient group.

MDB-43. SHARED DECISION-MAKING (SDM) REGARDING RADIATION-AVOIDING (RA) THERAPY IN YOUNG CHILDREN WITH MEDULLOBLASTOMA (MB)

Abstract BACKGROUND Standard treatment for MB in patients age ≥ 3 years includes craniospinal radiation with tumor bed boost and chemotherapy. Radiation carries substantial risk of long-term issues, particularly in the youngest patients: second malignancy, neurocognitive issues, vasculopathy and endocrinopathies. Numerous trials have attempted to decrease or avoid the use of radiation by intensifying chemotherapy, some using high dose chemotherapy with autologous hematopoietic stem cell rescue (HDC). One of the most successful RA protocols, Children’s Oncology Group ACNS0334 enrolled children age &amp;lt; 36 months and treated with 3 cycles of induction (+/- high dose methotrexate) and 3 cycles HDC without planned radiation. Since 2012, we offer SDM with caregivers regarding treatment of their children ages 3-7 years with MB. Caregivers may choose standard radiation and chemotherapy (SRC) or the RA treatment above. OBJECTIVE Describe patient and disease characteristics and outcomes in patients aged 3-7 years treated for MB with SDM regarding the use of radiation. METHODS Retrospective analysis of diagnosis, treatment and clinical outcomes in all children &amp;lt;8 y.o. who completed treatment for MB between 2012 and 2023. RESULTS There were 16 patients offered SDM (all gross total resection without metastases) 7 chose RA and 9 SRC. The SRC group was enriched with molecularly high-risk patients (4 MYC or MYCN amplification, 1 SHH with P53 mutation). In the RA group, relapse occurred in 14% (n=1 of 7). In the SRC group, 44% relapsed (n=4 of 9). One patient developed high-grade glioma in the radiation boost field 10 years later. There was 1 death in the RA group due to disease progression and 5 deaths in the SRC group, 1 due to second malignancy. CONCLUSIONS We report excellent survival with RA therapy for appropriately selected young children (age 3-7 years) when SDM is used with families to determine the best treatment for their child.

The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial

AimThe cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. Materials and methodsThis prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. Key findings174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed – 269] vs. 160 m [IQR: not performed – 252], p = 0.80 and 400 m [IQR: 299–461] vs. 375 m [IQR: 65–441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SignificanceA perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

Protected cardiac surgery: strategic mechanical circulatory support to improve postcardiotomy mortality.

To examine the evolving landscape of cardiac surgery, focusing on the increasing complexity of patients and the role of mechanical circulatory support (MCS) in managing perioperative low cardiac output syndrome (P-LCOS). P-LCOS is a significant predictor of mortality in cardiac surgery patients. Preoperative risk factors, such as cardiogenic shock and elevated lactate levels, can help identify those at higher risk. Proactive use of MCS, rather than reactive implementation after P-LCOS develops, may lead to improved outcomes by preventing severe organ hypoperfusion. The emerging concept of "protected cardiac surgery" emphasizes early identification of these high-risk patients and planned MCS utilization. Additionally, specific MCS strategies are being developed and refined for various cardiac conditions, including AMI-CS, valvular surgeries, and pulmonary thromboendarterectomy. This paper explores the shifting demographics and complexities in cardiac surgery patients. It emphasizes the importance of proactive, multidisciplinary approaches to identify high-risk patients and implement early MCS to prevent P-LCOS and improve outcomes. The concept of protected cardiac surgery, involving planned MCS use and shared decision-making, is highlighted. The paper also discusses MCS strategies tailored to specific cardiac procedures and the ethical considerations surrounding MCS implementation.

Enhancing mortality prediction after coronary artery bypass graft: a machine learning approach utilizing EuroScore.

Aim: We developed a machine learning model using EuroScore assumptions and preoperative and intraoperative risk factors to predict mortality after coronary artery bypass graft (CABG). Materials & methods: We retrospectively examined data from 108 CABG patients at King Abdullah University Hospital, classifying them into risk groups via EuroScore and predicting mortality through random forest classification. Results: High-risk patients displayed longer surgical times and significant factors such as age and surgery choice. The median EuroScore was 0.95 (0.5-6.4). The model yielded high AUC scores (0.98, 0.95) indicating strong predictive accuracy. Conclusion: Our findings showed that the machine learning models combined with the EuroScore significantly improve post-CABG mortality prediction. For further validation, larger datasets are needed.

A comparative study between curb-65 and psi/port score as predictors for ICU admission and mortality in community acquired pneumonia patients presenting to a tertiary care hospital

Despite recent advances in clinical medicine, mortality due to CAP has remained relatively the same. Therefore, early recognition for ICU admission plays a pivotal role in management of CAP. PSI/PORT (Pneumonia Severity Index/ Pneumonia Patient Outcome Research Team) score and CURB-65 (Confusion, Uremia, Respiratory rate, BP, Age &amp;#62; 65 years) are the two severity assessment scores that have extensively been used by the clinicians to distinguish between high risk and low risk patients. This study aims at comparing the predictive value of these two scores for ICU admission and mortality. The information required for calculating CURB-65 and PSI was extracted with careful history taking, patient assessment and necessary investigations. Patients with &amp;#62;18 years of age, diagnosed clinically and radiologically with CAP were included in the study.CURB-65 and PSI scores were determined in a total of 131 patients on admission. Based on careful clinical assessment and judgment of treating physician 60 patients were admitted in ICU whereas 71 patients were admitted in medical ward. Out of 60 patients admitted in ICU 23 died. The ability to predict ICU admission was almost similar for PSI/PORT score (AUC 0.9605; 95% CI 0.9277-0.9933) and CURB-65 (AUC 0.9694; 95% CI 0.9368-1.9714). The ability to predict mortality was almost similar for PSI/PORT score (AUC 0.9196; 95% CI 0.8670-0.9722) and CURB-65 (AUC 0.9214 95% CI 0.8696-0.9732). CURB-65 score was found almost similar in predicting ICU admission amongst patients coming with CAP to our hospital when compared to PSI/PORT score and when predicting mortality in patients with community-acquired pneumonia, CURB-65 and PSI/PORT score appear to have comparable specificity and sensitivity. Considering the simplicity, CURB-65 score could be preferred over PSI/PORT score. However, larger studies are required to know the exact Indian scenario. Despite of recent advances in the field of medical science the mortality due to CAP has remained relatively the same. Therefore, early diagnosis and admission to ICU with standard treatment play a pivot role in management of patients with CAP. Two scoring system, PSI/PORT score and CURB-65 score, are widely being used to differentiate between low risk and high risk patients. We undertook this study for comparing the predictive value of these two scores for ICU admission and mortality.

Dabigatran for Dental Procedures in Patients with High Risk Bleeding

Background: Management of patients with high risk of bleeding during oral and dental procedures faces many challenges. The aim of this study was review strategies for facing high risk of bleeding patients taking dabigatran under dental procedure. Methods: Articles and scientific texts will be searched in the six main databases, such as PubMed, Scopus, Web of Science, Science Direct, Google Scholar and Cochrane Library from 2007 to 2022, with keywords “dabigatran” AND “bleeding” AND “dental procedures” OR “dental care”. The inclusion criteria for articles included in the study were papers published about treatment patients with dabigatran and undergoing a dental procedure, English language and design of case reports, case series, quasi-experimental studies and clinical trials. This study was performed using PRISMA. Results: At first, 43 references included and finally 8 articles that met the inclusion criteria were select. CASP and STORBE checklists used for quality evaluation. Two reviewers checked eligibility of the selected articles, separately. Challenging Controversial results were found in selected studies. 4 studies demonstrated that Dabigatran should be interrupted at least 12 hours before invasive dental procedures. Some studies highlight that discontinuing Dabigatran depends on the patient's renal function. Also, it showed that deciding whether to stop Dabigatran or not by cardiologists determine based on elective or emergency high-risk patients. Conclusions: Based on the results of the included studies, it is better to decide to stop or continue dabigatran before any dental treatment based on the type of intervention, the risk of bleeding and the patient's clinical situation. However, is preferred to discontinue taking this drug in high risk of bleeding dental procedures.

Dabigatran for Dental Procedures in Patients with High Risk Bleeding

Background: Management of patients with high risk of bleeding during oral and dental procedures faces many challenges. The aim of this study was review strategies for facing high risk of bleeding patients taking dabigatran under dental procedure. Methods: Articles and scientific texts will be searched in the six main databases, such as PubMed, Scopus, Web of Science, Science Direct, Google Scholar and Cochrane Library from 2007 to 2022, with keywords “dabigatran” AND “bleeding” AND “dental procedures” OR “dental care”. The inclusion criteria for articles included in the study were papers published about treatment patients with dabigatran and undergoing a dental procedure, English language and design of case reports, case series, quasi-experimental studies and clinical trials. This study was performed using PRISMA. Results: At first, 43 references included and finally 8 articles that met the inclusion criteria were select. CASP and STORBE checklists used for quality evaluation. Two reviewers checked eligibility of the selected articles, separately. Challenging Controversial results were found in selected studies. 4 studies demonstrated that Dabigatran should be interrupted at least 12 hours before invasive dental procedures. Some studies highlight that discontinuing Dabigatran depends on the patient's renal function. Also, it showed that deciding whether to stop Dabigatran or not by cardiologists determine based on elective or emergency high-risk patients. Conclusions: Based on the results of the included studies, it is better to decide to stop or continue dabigatran before any dental treatment based on the type of intervention, the risk of bleeding and the patient's clinical situation. However, is preferred to discontinue taking this drug in high risk of bleeding dental procedures.